A microfluidic model of the blood–brain barrier to study permeabilization by pulsed electric fields

Abstract

Pulsed electric fields interact with the blood–brain barrier (BBB) and have been shown to increase the BBB permeability under some pulsing regimes. Pulsed electric fields may enhance drug delivery to the brain by disrupting the integrity of the BBB and allowing otherwise impermeable drugs to reach target areas. Microfluidic, in vitro models offer an alternative platform for exploring the impact of pulsed electric fields on the BBB because they create physiologically relevant microenvironments and eliminate the confounding variables of animal studies. We developed a microfluidic platform for real-time measurement of BBB permeability pre- and post-treatment with pulsed electric fields. Permeability is measured optically by the diffusion of fluorescent tracers across a monolayer of human cerebral microcapillary endothelial cells (hCMECs) cultured on a permeable membrane. We found that this device is able to capture real-time permeability of hCMEC monolayers for both reversible and irreversible electroporation pulsing regimes. Furthermore, preliminary testing of deep brain stimulation pulsing regimes reveals possible impacts on BBB integrity. This device will enable future studies of pulsed electric field regimes for improved understanding of BBB permeabilization.